This work proposes to examine the cardiac effects of extracellular pH at a cellular level using monolayer cultures of myocardial cells. These cells, derived from the ventricles of 1-2 day old rats, continue to show spontaneous rhythmic contractions in vitro. The chronotropic and inotropic effects of changes in extracellular pH will be determined from photo-optical recordings of the rate, magnitude and velocity of the contractile response in these cells. This will be accompanied by a determination of the influence of pH on sodium, potassium and calcium membrane exchange in an attempt to define ionic correlates of pH induced changes in contractility. Cellular ionic contents and fluxes will be measured using the appropriate radioisotope tracers. The effects on the contractile and ionic behaviour of the cells of both acute and long-term (several hours) pH change will be measured. The study further proposes to evaluate the influence of the positive inotropic drugs, ouabain, isoproterenol and dopamine on the inotropic and ionic responses of the myocardial cells to variation in extracellular pH. Since extracellular pH may affect automaticity of cardiac tissue, and so induce arrhythmias, the effect of antiarrhythmic drugs (quinidine, lidocinae and propranolol) on the chronotropic behaviour of the cells, and its ionic basis at different pH levels, will be determined. The studies should yield further information as to (a) the cellular basis for pH dependent changes in cardiac function, and (b) the ability of drugs to counter both the chronotropic and inotropic effects and their ionic correlates. This information will improve the overall understanding of the disease process and lead to an improved therapeutic approach.